2017 ASCO Annual Meeting!
Session: Translating Tumor Sequencing Into Clinical Decision-Making: The Record to Date
Type: Clinical Science Symposium
Time: Saturday June 3, 8:00 AM to 9:30 AM
Location: Hall D1
Clinical application of comprehensive next generation sequencing in the management of metastatic cancer in adults.
2017 ASCO Annual Meeting
J Clin Oncol 35, 2017 (suppl; abstr 101)
Author(s): Erin Frances Cobain, Dan R. Robinson, Yi-Mi Wu, Jessica Everett, Erica Rabban, Chandan Kumar, Scott Schuetze, Ajjai Shivaram Alva, Rashmi Chugh, Francis P. Worden, Mark Zalupski, Scott A. Tomlins, Nithya Ramnath, Anne F. Schott, Elena Martinez Stoffel, David C. Smith, Lakshmi Priya Kunju, Daniel F. Hayes, Moshe Talpaz, Arul M. Chinnaiyan; University of Michigain Health System, Ann Arbor, MI; Pathology Department, University of Michigan, Ann Arbor, MI; University of Michigan, Ann Arbor, MI; University of Michigan Center for Translational Pathology, Ann Arbor, MI; University of Michigan Health System, Ann Arbor, MI; Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI
Background: Next generation sequencing (NGS) platforms are frequently utilized in the care of patients (pts) with metastatic cancer to identify tumor genomic alterations that may serve as therapeutic targets. Biomarker driven clinical trials, such as NCI-Molecular Analysis for Therapy Choice (MATCH) and Targeted Agent and Profiling Utilization Registry (TAPUR) have augmented clinicians’ ability use this strategy in clinical practice. Methods: From 2011-2015 over 500 adult pts with metastatic solid tumors of diverse lineage underwent biopsy for whole exome and transcriptome sequencing of tumor and matched normal sample through the Michigan Oncology Sequencing Center (Mi-Oncoseq). Genomic alterations identified were reviewed at Precision Medicine Tumor Board and tiered according to their clinical relevance. Alterations were also classified as being identifiable or not identifiable by a commercially available NGS assay such as Oncomine Focus or FoundationOne. Results: Genomic alterations identified by Mi-Oncoseq provided rationale for enrollment in a clinical trial in 72% (n = 360) of cases. The percentage of pts who did receive therapy informed by NGS results increased over time (5% in 2012 versus 11% in 2015). 11% of pts (n = 55) had a pathogenic germline variant (PGV) conferring increased cancer risk identified, none of which were known prior to study entry. Numerous pts had clinically relevant molecular alterations identified by Mi-Oncoseq that would not have been identifiable utilizing targeted NGS assays, including PGVs and activating/deleterious gene fusions. Conclusions: Comprehensive NGS, including DNA and RNA sequencing, readily identifies potentially actionable alterations in the vast majority of pts beyond what is observed with use of targeted NGS platforms. Observed modest increase in utilization of NGS results to direct subsequent therapy over time is due to clinician employment of this strategy earlier in the therapeutic algorithm, increased availability of biomarker driven clinical trials and changes in physician referral patterns. Comprehensive NGS identified many unanticipated PGVs of clinical importance for pts and their families. Clinical trial information: HUM00067928.
3. Genomic profiling of resistant tumor samples following progression on EGF816, a third generation, mutant-selective EGFR tyrosine kinase inhibitor (TKI), in advanced non-small cell lung cancer (NSCLC).